Direclidine

INGREZZA® (valbenazine) Third Quarter Net Product Sales of $613 Million Representing 26% Year-Over-Year Growth INGREZZA ® (valbenazine) 2024 Net Product Sales Guidance Raised to $2.30 - $2.32 Billion Board Authorizes $300 Million Share Repurchase Plan SAN DIEGO, Oct. 30, 2024 /PRNewswire/ -- Neurocrine Biosciences, Inc. (Nasdaq: NBIX) today announced its financial results for the third quarter ended September 30, 2024 and provided an update on its 2024 financial guidance. "With continued INGREZZA growth across the tardive dyskinesia and Huntington's disease chorea indications, FDA Priority Review for crinecerfont in congenital adrenal hyperplasia, a deep neuroscience focused pipeline and a strong balance sheet, we are confident in our ability to help more patients than ever before," said Kyle W. Gano, Ph.D., Chief Executive Officer of Neurocrine Biosciences. William Rastetter, Chairman of the Board of Directors of Neurocrine Biosciences, said, "The share repurchase authorization reflects the Board's confidence in Neurocrine's significant value creation potential. Importantly, the new share repurchase authorization preserves our flexibility to drive sustained growth through investments in INGREZZA and the anticipated launch of crinecerfont, while also advancing our diverse pipeline and maintaining our strong balance sheet." Financial Highlights INGREZZA Net Product Sales Highlights INGREZZA third quarter 2024 net product sales were $613 million and grew 26% compared to the third quarter 2023 Year-over-year growth driven by strong underlying patient demand and improvement in gross-to-net dynamics Other Key Financial Highlights Differences in third quarter 2024 GAAP and Non-GAAP operating expenses compared with third quarter 2023 were driven by: Increased R&D expense in support of an expanded and advancing portfolio including investments in muscarinic compounds, gene therapy programs, and second generation VMAT2 inhibitors. Third quarter 2024 R&D expense includes $39 million for development milestones achieved under collaborations with Nxera Pharma UK Limited (Nxera, formerly known as Sosei Heptares) and Voyager Therapeutics, Inc. (Voyager). Increased SG&A expense includes incremental investment in crinecerfont-related headcount, crinecerfont-related pre-launch activities, and continued investment in INGREZZA, including the recent expansion of our psychiatry and long-term care sales teams in September 2024. Third quarter 2024 GAAP net income and earnings per share were $130 million and $1.24, respectively, compared with $83 million and $0.82, respectively, for third quarter 2023 Third quarter 2024 Non-GAAP net income and earnings per share were $189 million and $1.81, respectively, compared with $156 million and $1.54, respectively, for third quarter 2023 Differences in third quarter 2024 GAAP and Non-GAAP net income compared with third quarter 2023 driven by: Higher INGREZZA net sales and improved operating margin Third quarter 2024 includes $17 million loss from changes in fair values of equity investments compared with $40 million loss for third quarter 2023 (Non-GAAP adjustment) Third quarter 2024 includes $39 million of expense for development milestones achieved under collaborations with Nxera and Voyager At September 30, 2024, the Company had cash, cash equivalents and marketable securities totaling approximately $1.9 billion A reconciliation of GAAP to Non-GAAP financial results can be found in Table 3 and Table 4 at the end of this news release. Recent Developments Kyle W. Gano, Ph.D. appointed Chief Executive Officer effective October 11, 2024. Announced the Company's Board of Directors has authorized a $300 million share repurchase plan. The Company subsequently intends to enter into a $300 million accelerated share repurchase transaction in the coming days, subject to market conditions, which will constitute the entirety of the authorized share repurchase plan. Announced positive topline data for the Phase 2 study of NBI-1117568, a first-in-class, orally active, highly selective investigational M4 agonist, in development as a potential treatment for schizophrenia. The successful completion of the Phase 2 study triggered a $35 million milestone payment to Nxera in the third quarter of 2024. We expect to advance NBI-1117568 into Phase 3 development in the first half of 2025, which would trigger an additional $15 million milestone payment to Nxera upon initiation of the Phase 3 study. Presented KINECT ®-HD2 interim data at the 2024 MDS International Congress of Parkinson's Disease and Movement Disorders demonstrating robust and sustained improvements in chorea associated with Huntington's Disease through week 104 irrespective of antipsychotic use. Announced the ERUDITE™ Phase 2 study of luvadaxistat (NBI-1065844) in cognitive impairment associated with schizophrenia (CIAS) did not meet its primary endpoint. In addition, we provided Takeda Pharmaceutical Company Limited with written notice of termination of the license agreement to develop and commercialize luvadaxistat and NBI-1065846. The termination is anticipated to be effective in April 2025. Provided Idorsia Pharmaceuticals Ltd. with written notice of termination of the license agreement to develop and commercialize NBI-827104 in epileptic encephalopathy with continuous spike and wave during sleep. The termination is anticipated to be effective in January 2025. Raised 2024 Net Sales Guidance and Updated Expense Guidance Conference Call and Webcast Today at 8:00 AM Eastern Time Neurocrine Biosciences will hold a live conference call and webcast today at 8:00 a.m. Eastern Time (5:00 a.m. Pacific Time). Participants can access the live conference call by dialing 800-225-9448 (US) or 203-518-9708 (International) using the conference ID: NBIX. The webcast and accompanying slides can also be accessed at approximately 8:00 a.m. Eastern Time on Neurocrine Biosciences' website under Investors at . A replay of the webcast will be available on the website approximately one hour after the conclusion of the event and will be archived for approximately one month. About Neurocrine Biosciences Neurocrine Biosciences is a neuroscience-focused, biopharmaceutical company with a simple purpose: to relieve suffering for people with great needs, but few options. We are dedicated to discovering and developing life-changing treatments for patients with under-addressed neurological, neuroendocrine, and neuropsychiatric disorders. The company's diverse portfolio includes FDA-approved treatments for tardive dyskinesia, chorea associated with Huntington's disease, endometriosis* and uterine fibroids*, as well as a robust pipeline including multiple compounds in mid- to late-phase clinical development across our core therapeutic areas. For three decades, we have applied our unique insight into neuroscience and the interconnections between brain and body systems to treat complex conditions. We relentlessly pursue medicines to ease the burden of debilitating diseases and disorders, because you deserve brave science. For more information, visit neurocrine.com, and follow the company on LinkedIn, X (Formerly Twitter) and Facebook. (*in collaboration with AbbVie) NEUROCRINE BIOSCIENCES, NEUROCRINE and YOU DESERVE BRAVE SCIENCE are registered trademarks of Neurocrine Biosciences, Inc. The Neurocrine logo is a trademark of Neurocrine Biosciences, Inc. Non-GAAP Financial Measures In addition to the financial results and financial guidance that are provided in accordance with accounting principles generally accepted in the United States (GAAP), this press release also contains the following Non-GAAP financial measures: Non-GAAP R&D expense, Non-GAAP SG&A expense, and Non-GAAP net income and net income per share. When preparing the Non-GAAP financial results and guidance, the Company excludes certain GAAP items that management does not consider to be normal, including recurring cash operating expenses that might not meet the definition of unusual or non-recurring items. In particular, these Non-GAAP financial measures exclude: non-cash stock-based compensation expense, charges associated with convertible senior notes, vacated legacy campus facility costs, net of sublease income, non-cash amortization expense related to acquired intangible assets, acquisition and integration costs, changes in fair value of equity security investments, changes in foreign currency exchange rates and certain adjustments to income tax expense. These Non-GAAP financial measures are provided as a complement to results provided in accordance with GAAP as management believes these Non-GAAP financial measures help indicate underlying trends in the Company's business, are important in comparing current results with prior period results and provide additional information regarding the Company's financial position. Management also uses these Non-GAAP financial measures to establish budgets and operational goals that are communicated internally and externally and to manage the Company's business and evaluate its performance. The Company provides guidance regarding combined R&D and SG&A expenses on both a GAAP and a Non-GAAP basis. A reconciliation of these GAAP financial results to Non-GAAP financial results is included in the attached financial information. Forward-Looking Statements In addition to historical facts, this press release contains forward-looking statements that involve a number of risks and uncertainties. These statements include, but are not limited to, statements related to: the benefits to be derived from our products and product candidates; the value our products and/or our product candidates may bring to patients; the continued success of INGREZZA; our financial and operating performance, including our future revenues, expenses, or profits; our collaborative partnerships; expected future clinical and regulatory milestones; the timing of the initiation and/or completion of our clinical, regulatory, and other development activities and those of our collaboration partners; and our intention to enter into an accelerated share repurchase transaction, including the expected dollar amounts and the timing of the transaction. Among the factors that could cause actual results to differ materially from those indicated in the forward-looking statements are: our future financial and operating performance; risks and uncertainties associated with the commercialization of INGREZZA; risks that the crinecerfont New Drug Applications (NDAs) may not obtain regulatory approval, such approval may be delayed, or may not receive the benefits associated with priority review; risks related to the development of our product candidates; risks associated with our dependence on third parties for development, manufacturing, and commercialization activities for our products and product candidates, and our ability to manage these third parties; risks that the FDA or other regulatory authorities may make adverse decisions regarding our products or product candidates; risks that clinical development activities may not be initiated or completed on time or at all, or may be delayed for regulatory, manufacturing, or other reasons, may not be successful or replicate previous clinical trial results, may fail to demonstrate that our product candidates are safe and effective, or may not be predictive of real-world results or of results in subsequent clinical trials; risks that the potential benefits of the agreements with our collaboration partners may never be realized; risks that our products, and/or our product candidates may be precluded from commercialization by the proprietary or regulatory rights of third parties, or have unintended side effects, adverse reactions or incidents of misuse; risks associated with government and third-party regulatory and/or policy efforts which may, among other things, impose sales and pharmaceutical pricing controls on our products or limit coverage and/or reimbursement for our products; risks associated with competition from other therapies or products, including potential generic entrants for our products; constraints, volatility, or disruptions in the capital markets or other factors affecting our ability to enter into or complete an accelerated share repurchase transaction; and other risks described in our periodic reports filed with the SEC, including our Quarterly Report on Form 10-Q for the quarter ended September 30, 2024. Neurocrine Biosciences disclaims any obligation to update the statements contained in this press release after the date hereof other than as required by law. SOURCE Neurocrine Biosciences, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

百时美施贵宝的精神分裂症新药Cobenfy（xanomeline/trospium，即KarXT）于今年9月底顺利获得FDA批准，是几十年来精神分裂症领域首个新型作用机制的药物（M1/M4毒蕈碱激动剂）。 就在获得批准前夕，杰富瑞(Jefferies)分析师预测，Cobenfy仅精神分裂症适应症的年销售额最高将达到35亿美元，所有适应症的销售额将达到62亿美元。高盛分析师预测，到2035年，Cobenfy精神分裂症销售额将达到37亿美元。 Cobenfy作为其他精神分裂症药物的辅助药物正在进行Ⅲ期试验，预计将于2025年获得结果；治疗阿尔茨海默病精神病Ⅲ期试验预计将于2026年获得数据。百时美施贵宝还计划启动Cobenfy治疗双相情感障碍、阿尔茨海默病相关躁动和阿尔茨海默病的试验。Cobenfy已计划于2025年启动与自闭症相关的认知障碍研究项目，并计划于2025年底或2026年初启动另一个针对与自闭症相关烦躁的研究项目。 尽管精神分裂症市场有超过20种抗精神病药物可供患者选择，似乎已经非常饱和，但是患者对现有治疗药物非常不满意，主要原因是这些抗精神病药物只对大约30%的患者有效。 与传统针对多巴胺2（D2）受体的非典型抗精神病药物相比，Cobenfy具有差异化的疗效、安全性和耐受性，有望成为该治疗领域游戏规则的改变者。 延伸阅读：70年来精神分裂症First in Class新药KarXT将于9月下旬获FDA批准 与此同时，在精神分裂症新药研发管线中，除了传统抗精神病药物外，Cobenfy还面临着同类机制的追赶者、新机制的突破者以及505(b)(2)挑战者。 追赶者：直接数据PK NBI-1117568 就在今年8月底，Neurocrine公司公布了其开发的口服选择性M4毒蕈碱激动剂NBI-1117568Ⅱ期临床试验结果：尽管该药物可改善精神分裂症的症状，但只有在最低剂量达到主要终点。即每日一次 20 mg 剂量治疗第 6 周时阳性和阴性症状量表 (PANSS) 总分较基线有临床意义和统计学显着降低，安慰剂调整后平均降低 7.5 分；在此剂量水平下，疾病的严重程度也得到了改善。所有其他剂量组（30mg、40mg和60mg）均未达到试验的主要终点。 该公司股价在结果公布后下跌了20%，部分原因是其PANSS评分低于竞争对手。 Cobenfy在3项关键的Ⅲ期临床试验（EMERGENT-1、2、3）主要终点方面，EMERGENT-3中治疗第五周PANSS总分降低了8.4分，略低于EMERGENT-2中的9.6分和EMERGENT-1的11.6分。 Neurocrine仍旧计划于2025年初把NBI-1117568推进到Ⅲ期临床试验，未来试验数据有待于进一步观察。 不过，该公司还具有丰富的毒蕈碱激动剂组合：M1激动剂NBI-1117567、M4激动剂NBI-1117569和M1/M4双重激动剂NBI-1117570都正在进行Ⅰ期临床试验。Neurocrine在未来有充足的选择机会。 Emraclidine 艾伯维于2023年12月以87亿美元收购Cerevel，从而获得了M4毒蕈碱激动剂Emraclidine，目前处于II期EMPOWER - 2研究开发阶段。不过该研究因为比一般的II期试验规模大得多（招募372例患者），因此被认为具有可用于上市申请潜力。 根据2022年发表于《柳叶刀》杂志上的Ⅰb期试验结果，Emraclidine对精神分裂症成年人治疗六周后PANSS总分出现了具有临床意义和统计学意义的改善。 突破者：多种机制齐出击 ALTO-101 Alto Neuroscience正在开发的新型磷酸二酯酶4(PDE4)酶抑制剂ALTO-101来治疗精神分裂症认知症状。 PDE4抑制剂已获批上市用于治疗慢性阻塞性肺病（COPD ）和银屑病。有趣的是，PDE4酶在大脑中高表达，被认为是治疗神经系统疾病的潜在靶点。 Alto于2024年6月启动了ALTO-101的II期研究，计划招募约70名年龄在21至55岁精神分裂症和明显认知障碍的患者。预计2025年下半年将获得主要数据。 在I期研究中，该候选药物对认知和与认知功能相关的脑电图(EEG)测量结果表现出积极作用。该公司报告称，ALTO-101透皮制剂比口服制剂具有更大的全身药物暴露量。透皮ALTO-101将在Ⅱ期试验中进行测试。 MK-8189 PDE10A是一种主要存在于纹状体多巴胺能神经元中的磷酸二酯酶，可终止多巴胺与D1和D2受体结合所诱导的细胞内信号，因此，被认为是治疗精神分裂症的潜在靶点。 默沙东也在开发的治疗精神分裂症的强效选择性PDE10A抑制剂MK-8189。MK-8189在随机概念验证临床试验的初步结果表明：与安慰剂相比，MK-8189在治疗4周后患者PANSS总分相对于基线的变化呈改善趋势。目前正处于Ⅱb期临床开发阶段。 延伸阅读：辉瑞、武田、灵北“三连败”后：默沙东MK-8189初步看到更广泛潜力 Iclepertin 勃林格殷格翰正在开发一种甘氨酸转运蛋白1(GlyT1)抑制剂iclepertin，用于治疗与精神分裂症相关的认知症状。GlyT1被认为在调节抑制性和兴奋性神经传递方面发挥重要作用。 Ⅱ期临床试验结果显示，与安慰剂相比，Iclepertin 2-25 mg剂量组患者的认知功能均较基线改善，其中10 mg和25 mg组患者的认知功能改善幅度最大。所有剂量的Iclepertin总体安全性及耐受性都是良好的。 iclepertin目前正在进行三项大型随机对照Ⅲ期临床试验研究，预计将于2025年公布结果。 505(b)(2)挑战者：最直接威胁 不过，对于百时美施贵宝，Cobenfy最为直接的挑战者可能是Terran Biosciences。 由于Cobenfy两种活性成分xanomeline和trospium都属于“老药”，化合物已失去专利保护。 Terran Biosciences公司正在通过开发xanomeline和trospium前药的组合，有望在未来挑战百时美施贵宝。 为了成功克服xanomeline和trospium的药代动力学局限性，Terran组建了一支由全球药物化学专家组成的团队，设计了10000多种新型前药。Terran的PK建模团队针对各种不同的配方设计和释放曲线开发了xanomeline和trospium的预测模型，以确定最佳药代动力学参数和比例。Terran利用200名化学家组成的团队合成了500多种前药，然后进行了临床前测试，包括285项体外研究和365项体内研究。 Terran目前正在开发Cobenfy的两种前药版本，一种是每日一次的口服候选药物TerXT，另一种是数月注射剂TerXT LAI。长效注射剂可以大大改善精神分裂症患者服药依从性问题。   Terran已通过505(b)(2)审批途径将TerXT提交给FDA申请，目前正在接受FDA审查。 Terran正计划分别针对两个版本启动两项I期试验，以确认安全性和药代动力学。不过，该公司仍需要等待百时美施贵宝的五年市场独占期结束，才能将其产品推向市场。新的制药化学实体从FDA批准开始，将获得五年的市场独占期，以防止仿制药竞争。 当药物的原始成分专利到期时，制药公司可以开发药物前体版本，以绕过原始药物配方或组合的任何其他专利。开发药物前体会创造一种新的可获得专利授权保护的分子，使公司能够重新获得该药物前体的20年专利保护。只要原始成分专利到期，药物前体就可以获得批准和上市，而不会受到原始药物配方其他专利的阻碍。 今年5月20日，Terran称已收到美国专利商标局 (USPTO) 专利权利要求保护全球首款xanomeline前药的物质成分专利申请通知。 备注：本文同时刊载于《医药经济报》，有删改。 本文由「新药前沿」微信公众号根据公开资料整理编辑，欢迎个人转发至朋友圈。媒体或机构转载授权请在「新药前沿」微信公众号留言公众号名称，审核通过后开通白名单获取转载授权，转载请标识来源。 免责声明：本文仅作信息交流之目的，非投资建议或者治疗方案推荐，「新药前沿」微信公众号不对任何主体因使用本文内容而导致的任何损失承担责任。 限于作者水平和专业知识所限，如有谬误，欢迎指正！